Fat storage-inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes

Madhur Agrawal, Chia Rou Yeo, Asim Shabbir, Vanna Chhay, David L Silver, Faidon Magkos, Antonio Vidal-Puig, Sue-Anne Toh

1 Citation (Scopus)

Abstract

Fat storage-inducing transmembrane protein 2 (FIT2) aids in partitioning of cellular triacylglycerol into lipid droplets. A genome-wide association study reported FITM2-R3H domain containing like-HNF4A locus to be associated with type 2 diabetes (T2DM) in East Asian populations. Mice with adipose tissue (AT)-specific FIT2 knockout exhibited lipodystrophic features,with reduced ATmass, insulin resistance, and greater inflammation in AT when fed a high-fat diet. The role of FIT2 in regulating human adipocyte function is not known.Here,we found FIT2 protein abundance is lower in subcutaneous and omental AT obtained from patients with T2DM compared with nondiabetic control subjects. Partial loss of FIT2 protein in primary human adipocytes attenuated their lipid storage capacity and induced insulin resistance. After palmitate treatment, triacylglycerol accumulation, insulininduced Akt (Ser-473) phosphorylation, and insulin-stimulated glucose uptake were significantly reduced in FIT2 knockdown adipocytes compared with control cells.Gene expression of proinflammatory cytokines IL-18 and IL-6 and phosphorylation of the endoplasmic reticulumstressmarker inositol-requiring enzyme1awere greater in FIT2 knockdown adipocytes than in control cells.Our results showfor the first time that FIT2 is associatedwith T2DMin humans and plays an integral role in maintaining metabolically healthy AT function.

Original languageEnglish
JournalF A S E B Journal
Volume33
Issue number1
Pages (from-to)430-440
Number of pages11
ISSN0892-6638
DOIs
Publication statusPublished - Jan 2019
Externally publishedYes

Fingerprint

Dive into the research topics of 'Fat storage-inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes'. Together they form a unique fingerprint.

Cite this